Understanding the exact cell-type composition in the different regions of the mouse brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell-types present in the mouse brain have been defined through a handful of specific markers, the different subtypes within these categories, as well as their location and connectivity are far from understood. Epigenomic signatures such as DNA methylation (mC) and open chromatin are stable modifications that persist in post-mitotic cells throughout their lifetime, defining their cellular identity. Open chromatin as well as methylation patterns are cell type specific, differentiating the major types of cells i.e., neurons and glia, in the rodent and human cortex, as well as differentiating neuronal types in mouse brain. Research Segment 1 of this center proposes to produce a catalog of methylation and open chromatin patterns at the single-cell level throughout the entire mouse brain. Analysis of the combined data will permit the discovery of cell-type specific regulatory regions that will allow the production of transgenic mouse lines and viral tools that will become available to the community.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH114831-04
Application #
9941137
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Mukamel, Eran A; Ngai, John (2018) Perspectives on defining cell types in the brain. Curr Opin Neurobiol 56:61-68
Preissl, Sebastian; Fang, Rongxin; Huang, Hui et al. (2018) Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation. Nat Neurosci 21:432-439
Yoon, Young-Sil; Tsai, Wen-Wei; Van de Velde, Sam et al. (2018) cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis. Proc Natl Acad Sci U S A 115:E5289-E5297
Luo, Chongyuan; Rivkin, Angeline; Zhou, Jingtian et al. (2018) Robust single-cell DNA methylome profiling with snmC-seq2. Nat Commun 9:3824
Luo, Liqun; Callaway, Edward M; Svoboda, Karel (2018) Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron 98:865
Luo, Liqun; Callaway, Edward M; Svoboda, Karel (2018) Genetic Dissection of Neural Circuits: A Decade of Progress. Neuron 98:256-281
Luo, Chongyuan; Hajkova, Petra; Ecker, Joseph R (2018) Dynamic DNA methylation: In the right place at the right time. Science 361:1336-1340